Process for para-methylolating phenol compounds

ABSTRACT

A process for preparing phenols with high selectivities, comprising reacting a phenol compound and a formaldehyde source with a quaternary ammonium as a counter cation of a phenol anion in the presence of an alcoholic organic solvent.

TECHNICAL FIELD

The present invention relates to a process for para-methylolating phenolcompounds. More specifically, the present invention relates to a processfor para-methylolating phenol compounds, comprising reacting a phenolcompound with a formaldehyde source under a basic condition.

Phenol compounds of which the para-position has been hydroxymethylatedare important as a variety of organic compounds such as medicines,agricultural agents and anti-oxidants or as raw materials forsynthesizing them.

BACKGROUND ART

The ratio of para-/ortho-isomers in the synthesis of hydroxybenzylalcohols comprising reacting a phenol with formaldehyde in the presenceof a base catalyst is generally in the range of 1.0 or less. Thus, themain product of the reaction should be an o-hydroxybenzyl alcohol, andmany reports have been presented with reference to the process forselectively preparing the o-isomer for the purpose of promoting theformation thereof.

On the other hand, since p-hydroxybenzyl alcohol is a useful compound asdescribed above, some methods for increasing the product ratio have alsobeen proposed. For example, there are known two methods, (1) a methodfor reacting phenol with paraformaldehyde in the presence of a strongbasic catalyst and a polyalkylene ether (Japanese Patent Laid-OpenPublication No. 141423/1980), and (2) a method for reacting phenol withparaformaldehyde in the presence of an organic nitrogen compoundcontaining two or more nitrogen atoms in the molecule as a basiccatalyst. However, as far as the present inventor knows, the content ofthe p-isomer in the mixture of hydroxybenzyl alcohols are 49% and 47%,respectively, in these methods, and thus the ratio of the p-/o-isomersstill remains in the range no higher than 1.

Very recently, there has been reported a method for selectivelysynthesizing p-hydroxybenzyl alcohol with the use of cyclodextrin andsubstituted cyclodextrins (J. Chem. Soc., Chem. Commun., 652, 1988).This method, however, requires β-cyclodextrin, sodium hydroxide andformaldehyde in proportions of 20 to 40, of 50 and of 40, respectively,to the amount of phenol as a raw material, so that it can scarcely besaid to be an industrial method in view of the cost notwithstanding itshigh selectivity as the ratio of the p-/o-isomers is 15.7.

Japanese Patent Laid-Open Publication No. 106833/1989 also discloses asa method for selectively hydroxymethylating the p-position of asubstituted phenol a method for selectively synthesizing a phenol withthe use of cyclodextrin and substituted cyclodextrin. This method alsohas drawbacks in that it requires catalysts such as cyclodextrin andsodium hydroxide in excessive amounts to the substituted phenol and hasa low reaction velocity, so that it may be difficult to employ themethod in an industrial scale in consideration of its economy.

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide a process for preparingselectively an industrially useful p-hydroxybenzyl alcohols by aninexpensive method.

More specifically, the process for selectively para-methylolating aphenol according to the present invention comprises reacting a phenolcompound and a formaldehyde source in the presence of an alcoholicorganic solvent wherein a quaternary ammonium is used as a countercation of the anion of the phenol compound.

A quaternary ammonium salt, particularly a tetraalkylammonium salt, isgenerally used as a phase transfer catalyst, and a tetraalkylammoniumcation in organic synthesis is known to act as a super cation and tolead to many specific reactions. The present invention has surprisinglysucceeded in enhancing extensively the selectivity of a p hydroxybenzylalcohol with the use of the tetraalkylammonium cation.

That is, in the process according to the present invention, the ratio ofp-/o-isomers is larger than 1, often 2 or more. The material to be usedfor increasing the ratio, i.e., the quaternary ammonium cation, is notexpensive per se and used only in a small amount. Particularly when aquaternary ammonium type anion exchange resin is used as a quaternaryammonium cation, it may be reused, so that the economy of the process ofthe present invention is further improved.

BEST MODE FOR CARRYING OUT THE INVENTION Phenol Compounds

Phenol compounds to be methylolated according to the present inventionspecifically include phenol, 2-substituted phenols, 3-substitutedphenols, 3,5-disubstituted phenols, 2,5-disubstituted phenols,2,3-disubstituted phenols, 2,3,5-trisubstituted phenols and the like.Among these compounds, phenol and 2-substituted phenols are preferred.

In this connection, the substituents are optional and include, forexample, saturated or unsaturated aliphatic hydrocarbyl groups, aromatichydrocarbyl groups, alkoxy groups, hydroxyalkyl groups, a carboxylgroup, a sulfone group, an amino group, and halogens. Among thesesubstituents, the aliphatic hydrocarbyl groups, the alkoxy groups andhydroxyalkyl groups have preferably 6 or less carbon atoms, particularly4 or less carbon atoms.

Examples of typical substituted phenols are o-cresol, m-cresol,2-ethylphenol, 3-ethylphenol, 2,5-dimethylphenol, 2-phenylphenol,3-phenylphenol, guaiacol, 2-hydroxyphenethyl alcohol, 3-hydroxyphenethylalcohol, salicylic acid, 2-chlorophenol, and 2-bromophenol.

Formaldehyde Sources

As the formaldehyde sources which are reacted with the aforementionedphenols for introducing a methylol group into the phenolic rings,formalin, paraformaldehyde, hemiformals of lower alcohols, hemiformalsof polyhydric alcohols having, for example, 2 to 5 carbon atoms and thelike can be mentioned, among which paraformaldehyde and the hemiformalsof lower alcohols are preferred. Formalin may be used in a small amount,but the selectivity of the substitution on the phenolic ring topara-position tends to be decreased a little if the water content in thereaction system is increased. The term "formaldehyde source" in thepresent invention is used as a term which includes formaldehyde itself.Particularly, when formaldehyde purified from paraformaldehyde bysublimation is used, the reaction proceeds rapidly in a high yield whilesuppressing side-reaction.

Quaternary Ammonium Compounds

The quaternary ammonium compounds used in the present invention are thecompounds which are to become quaternary ammonium cations as the countercation of phenolates, preferably tetraalkyl ammonium cations. A group ofthe quaternary ammonium compounds of such a nature includestetraalkylammonium hydroxides which form tetraalkylammonium cations asthe counter cation of the phenolates, wherein the alkyl groups have 6 orless carbon atoms, preferably 4 or less carbon atoms. Specifically, thequaternary ammonium compounds include tetramethylammonium hydroxide,tetrabutylammonium hydroxide and the like. Another group of thepreferred quaternary ammonium compounds includes a hydroxide form of aquaternary ammonium salt type anion exchange resin.

The phenol compound and the quaternary ammonium compound are consideredto form a quaternary ammonium phenolate due to their ionic properties,and such a phenolate may be preliminarily formed prior to the methylolreaction or may be formed in situ. Thus, the aforementioned quaternaryammonium hydroxide can form a quaternary ammonium phenolate by theaddition of a phenol. Furthermore, if the quaternary ammonium compoundis a quaternary ammonium salt type anion exchange resin, a quaternaryammonium phenolate can be formed on the ion exchange resin by chargingthe Cl form of the resin into a column and anion exchanging by causing ametal phenolate such as sodium salt of a given phenol compound to flowfrom the top of the column.

Alcoholic Organic Solvents

The selective methylolation according to the present invention isperformed in the presence of an alcoholic organic solvent.

Examples of the alcoholic organic solvents suitable for use in theprocess of the present invention are (i) alkanols having carbon atoms ina range of the order of 1 to 10 such as methanol, ethanol, n-propanol,i-propanol, n-butanol and i-butanol; (ii) polyhydric alcohols havingcarbon atoms in a range of the order of 2 to 10 such as ethylene glycoland 2,3-butanediol; and (iii) alcohols having an aromatic ring such asbenzyl alcohol and the like, which are used alone or in admixturethereof within and/or between the groups. Among these solvents, loweralcohols preferably having 1 to 4 carbon atoms such as ethanol,n-propanol, i-propanol, i-butanol are preferred because these alcoholsprovide the para-methylolation reaction with increased selectivity andvelocity of the reaction.

The para-methylolation according to the present invention is conductedin the presence of an alcoholic organic solvent, which means that anon-alcoholic organic solvent can be used in admixture with thealcohols. As the non-alcoholic solvent which can be mixed, a variety oforganic solvents, for example (i) aromatic hydrocarbons such as benzene,toluene, and xylene, (ii) aliphatic hydrocarbons such as pentane,hexane, and heptane, (iii) halogenated alkyls such as chloroform,dichloromethane, and dichloroethane, (iv) amides such asdimethylacetamide and dimethylformamide, (v) sulfoxides such asdimethylsulfoxide, (vi) nitriles such as acetonitrile and benzonitrilecan be mentioned.

While the percentage ratio of the non-alcoholic solvent to be mixed isnot particularly limited as long as the alcoholic organic solvent has asubstantial effectiveness, it is preferably in the range no higher than70% by weight. If the non-alcoholic solvent is used in an amount greaterthan 70% by weight, the reaction velocity will tend to decrease. It isgenerally preferable to use a solvent comprising solely of an alcohol(alone or as a mixture of alcohols).

Reaction Condition

Provided that the para-methylolation is performed selectively with theuse of the aforedescribed raw materials for the reactions, the reactionconditions and the reaction operations can be any suitable ones.

Specifically, for example, if a tetraalkylammonium hydroxide is used asthe quaternary ammonium compound, the reaction is conducted so that thephenol compound in a proportion of 0.1 to 10 moles, preferably 0.5 to 3moles to 1 liter of the aforementioned solvent, the tetraalkylammoniumhydroxide is added in a proportion of 0.01 to 10 equivalents, preferably0.1 to 1.2 equivalents to the phenol compound and the formaldehydecompound is added in a proportion of 0.01 to 10 equivalents, preferably0.1 to 3 equivalents to the phenol compound.

Also, when the quaternary ammonium phenolate in which the Cl form of thequaternary ammonium salt type anion exchange resin has beenanion-exchanged with a sodium phenolate of a given phenol compound isused, the solvent is used in at least an amount to ensure that the resinparticles will be completely immersed in the solvent, and the reactionis conducted by adding thereto the formaldehyde source in a proportionof 0.01 to 10 equivalents, preferably 0.1 to 3 equivalents to thequaternary ammonium phenolate. The reaction temperature is in the rangeof 0° to 130° C., preferably 20° to 70° C.

The reaction time depends on the reaction temperatures and the kind ofsolvents, being ordinarily in the range of 24 to 72 hours at a reactiontemperature of 50° C. While the selectivity to the p-isomer is increasedsomewhat in the reaction at a lower temperature, the reaction rate islowered as well.

The reaction is generally conducted by stirring with heating under anitrogen atmosphere or heating in a sealed tube.

The methylol derivative, particularly the p-methylol derivative may berecovered from the reaction products by a conventional method.

EXAMPLES

The present invention is further described in detail below withreference to examples. In this connection, the analysis anddetermination of the reaction products were carried out by HPLC (highprecision liquid chromatography).

EXAMPLE 1

A commercially available 10% solution of tetramethylammonium hydroxidein methanol (manufactured by TOKYO KASEI CO.) was subjected to solventexchange with isopropanol to produce a solution of tetramethylammoniumhydroxide in isopropanol. To a 3.83 ml portion of the solution (2.24mmoles of tetramethylammonium hydroxide) was added 0.211 g of phenol(2.24 mmoles) to produce a solution of tetramethylammonium phenolate inisopropanol.

To the solution was added 2.48 ml of a paraformaldehyde-isopropanolsolution (1.12 mmoles as formaldehyde). The reaction system was purgedwith nitrogen, and stirring was conducted with heating at 50° C. for 115hours to complete the reaction.

The yield was 37.6% based on the formaldehyde.

The product was a mixture consisting of 81.6% of p-hydroxybenzylalcohol, 12.1% of o-hydroxybenzyl alcohol and 6.3% of dimethylol phenol.

At an initial stage of the reaction in which no dimethylol phenol hasyet been formed, p-hydroxybenzyl alcohol is in, a proportion of 87.1%and the ratio of p-/o-products is 6.75 at this stage.

EXAMPLE 2

To 5.53 ml of a commercially available 10% tetra-n-butylammoniumhydroxide-isopropanol solution (manufactured by TOKYO KASEI CO.; 1.69mmoles of tetra-n-butylammonium hydroxide) were added 1.87 ml of aparaformaldehyde-isopropanol solution (0.85 mmole as formaldehyde) and0.157 g of phenol (1.69 mmoles). The reaction system was purged withnitrogen, and stirring was conducted with heating at 50° C. for 20 hoursto complete the reaction.

The yield was 30.3% based on the formaldehyde.

The product was a mixture consisting of p-hydroxybenzyl alcohol,o-hydroxybenzyl alcohol and dimethylol phenol, and the proportion of thep-hydroxybenzyl alcohol was 75.9%.

At an initial stage of the reaction in which no dimethylol phenol hasyet been formed, p-hydroxybenzyl alcohol is in a proportion of 82.7% andthe ratio of p-/o-isomers is 4.79 at this stage.

COMPARATIVE EXAMPLE 1

The reaction was conducted in the system in Example 1 except that thecounter cation of phenol was sodium.

Phenol (0.211 g, 2.24 mmoles) and sodium hydroxide (0.094 g, 2.24mmoles) were added to 3.83 ml of isopropanol, and the mixture wasstirred with heating at 70° C. under a nitrogen atmosphere to form asolution. The reaction solution was cooled to room temperature, and 2.48ml of paraformaldehyde-isopropanol solution (1.12 mmoles offormaldehyde) was added to the reaction solution. The system was purgedwith nitrogen, and stirring was conducted with heating at 50° C. for 24hours to complete the reaction.

The yield was 38.1% based on the formaldehyde.

The product was a mixture consisting of three compounds, p-hydroxybenzylalcohol, o-hydroxybenzyl alcohol and dimethylol phenol, and theproportion of the p-hydroxybenzyl alcohol was 34.1%.

At an initial stage of the reaction in which no dimethylol phenol hasyet been formed, p hydroxybenzyl alcohol is in a proportion of 38.5% andthe ratio of p-/o-products is 0.63 at this stage.

EXAMPLE 3

A commercially available quaternary ammonium salt type anion exchangeresin ("DIAION SA10A" manufactured by Mitsubishi Chemical Industries,Ltd., strong base resin, gel form) was charged into a column and washedwith water. Then 0.5 mole/lit. of an aqueous sodium phenolate solutionwas caused to flow through the column to substitute a chloride ion witha phenolate ion. After the resin was washed with water within thecolumn, it was poured into a Buchner funnel, washed with water whilefiltration was carried out under suction to completely remove theexcessive amount of sodium phenolate, and further washed withisopropanol to remove water adhering to the resin.

To 10 ml of the phenolate form quaternary ammonium anion exchange resinthus prepared was added 3.5 ml of a paraformaldehyde-isopropanolsolution (2.35 mmoles of formaldehyde), and the mixture was heated at50° C. under a nitrogen atmosphere for 30 hours to complete thereaction.

The temperature was lowered to room temperature. The resin was pouredinto a column, and phenol derivatives were eluted with an aqueous 1N-HClsolution from the ion exchange resin. The product was a mixtureconsisting of p-hydroxybenzyl alcohol, o-hydroxybenzyl alcohol anddimethylol phenol, and the proportion of the p-hydroxybenzyl alcohol tothe total amount of the three compounds was 65.3%. At an initial stageof the reaction in which no dimethylol phenol has yet been formed,p-hydroxybenzyl alcohol is in a proportion of 74.1% and the ratio ofp-/o-isomers is 2.86 at this stage.

EXAMPLE 4

To 5.20 ml of a commercially available 10% tetramethylammoniumhydroxide-methanol solution (manufactured by TOKYO KASEI; 5.05 mmoleequivalents) was added 0.6264 g of guaiacol (5.05 mmoles), and methanolwas removed under reduced pressure. To the residue was added 10 ml ofisopropanol, and the alcohol was removed under reduced pressure again.Finally 5 ml of isopropanol was added to obtain about 7 ml of atetramethylammonium-2-methoxyphenolate-isopropanol solution (containing5.05 mmoles of guaiacol).

OPERATION 1

To the solution was added 3.78 ml of a solution in isopropanol offormaldehyde purified by sublimation (2.53 mmoles as formaldehyde), andthe mixture was purged with nitrogen and stirred with heating at 40° C.for 48 hours to complete the reaction.

The yield was 81.2% based on the formaldehyde.

The product was a mixture consisting of 4-hydroxymethyl-2-methoxyphenol,6-hydroxymethyl-2-methoxyphenol and 4,6-dihydroxymethyl-2-methoxyphenol,and the proportions of the three products were 80.2%, 10.3% and 9.5%,respectively. At an initial stage of the reaction in which no dimethylolderivative had yet been formed, the proportion of the4-hydroxymethyl-2-methoxyphenol relative to the product was 89.1%, andthe selectivity to the p-position of the reaction can thus be said to be89.1%.

COMPARATIVE EXAMPLE 2

In a 15-ml volume sealed pressure glass reactor were placed 5.0 ml ofisopropanol, 0.614 g of guaiacol (4.92 mmoles) and 0.209 g of sodiumhydroxide (4.92 mmoles). After the reactor was purged with nitrogen, themixture was stirred with heating at 80° C. to form a solution. After thetemperature was lowered to room temperature, 3.67 ml of a solution inisopropanol of formaldehyde purified by sublimation (2.46 mmoles asformaldehyde) was added, and the mixture was purged with nitrogen andstirred with heating at 50° C. for 14 hours to complete the reaction.

The yield was 97.6% based on the formaldehyde.

The product was a mixture consisting of 4-hydroxymethyl-2-methoxyphenol,6-hydroxymethyl-2-methoxyphenol and 4,6-dihydroxymethyl-2-methoxyphenol,and the proportions of the three products were 11.5%, 73.6% and 14.9%,respectively. At an initial stage of the reaction in which no dimethylolderivative had yet been formed, the percentage ratio of the4-hydroxymethyl-2-methoxyphenol to the product was 14.2%, and theselectivity to the p-position of the reaction can thus be said to be14.2%.

EXAMPLE 5

To 5.28 ml of a commercially available 10% tetramethylammoniumhydroxide-methanol solution (manufactured by TOKYO KASEI; 5.13 mmoleequivalents) was added 0.555 g of o-cresol (5.13 mmoles). About 7 ml ofa tetramethylammonium-2-methoxyphenolate-isopropanol solution(containing 5.13 mmoles of o-cresol) was obtained in the same manner asin Operation 1 in Example 4.

To the solution was added 3.84 ml of a solution in isopropanol offormaldehyde purified by sublimation (2.57 mmoles as formaldehyde), andthe mixture was purged with nitrogen and stirred with heating at 40° C.for 64 hours to complete the reaction.

The yield was 87.9% based on the formaldehyde.

The product was a mixture consisting of 4-hydroxymethyl-2-methylphenol,6-hydroxymethyl-2-methylphenol and 4,6-dihydroxymethyl-2-methylphenol,and the proportions of the three products were 85.1%, 8.1% and 6.8%,respectively. At an initial stage of the reaction in which no dimethylolderivative had yet been formed, the proportion of the 4hydroxymethyl-2-methylphenol relative to the product was 91.4%, and theselectivity to the p-position of the reaction can thus be said to be91.4%.

COMPARATIVE EXAMPLE 3

In a 15-ml volume sealed pressure glass reactor were placed 5.0 ml ofisopropanol, 0.555 g of o-cresol (5.13 mmoles) and 0.216 g of sodiumhydroxide (5.13 mmoles). After the reactor was purged with nitrogen, thecontent mixture was stirred with heating at 80° C. to form a solution.After the temperature was lowered to room temperature, 3.82 ml of asolution in isopropanol of formaldehyde purified by sublimation (2.56mmoles as formaldehyde) was added, and the mixture was purged withnitrogen and stirred with heating at 50° C. for 43 hours to complete thereaction.

The yield was 86.0% based on the formaldehyde.

The product was a mixture consisting of 4-hydroxymethyl-2-methylphenol,6-hydroxymethyl 2-methylphenol and 4,6-dihydroxymethyl-2-methylphenol,and the proportions of the three products were 25.6%, 53.8% and 20.6%,respectively. At an initial stage of the reaction in which no dimethylolderivative had yet been formed, the proportion of the 4-hydroxymethyl2-methylphenol relative to the product was 36.2%, and the selectivity tothe p-position of the reaction can thus be said to be 36.2%.

EXAMPLE 6

To 5.40 ml of a commercially available 10% tetramethylammoniumhydroxide-methanol solution (manufactured by TOKYO KASEI; 5.24 mmoleequivalents) was added 0.566 g of m-cresol (5.24 mmoles), and about 7 mlof a tetramethylammonium-3-methylphenolate isopropanol solution(containing 5.24 mmoles of m-cresol) was obtained in the same manner asin Operation 1 in Example 4.

To the solution was added 3.91 ml of a solution in isopropanol offormaldehyde purified by sublimation (2.62 mmoles as formaldehyde), andthe mixture was purged with nitrogen and stirred with heating at 40° C.for 120 hours to complete the reaction.

The yield was 90.4% based on the formaldehyde.

The product was a mixture consisting of 4-hydroxymethyl-3-methylphenol,6-hydroxymethyl-3-methylphenol and 2-hydroxymethyl-3-methylphenol anddimethylol derivatives such as 4,6-dihydroxymethyl-3-methylphenol andthe like. The proportions of the 4-hydroxymethyl-3-methylphenol relativeto the product was 70.4%. At an initial stage of the reaction in whichno dimethylol derivative had yet been formed, the proportion of the4-hydroxymethyl-3-methylphenol relative to the products was 79.6%, andthe selectivity to the p-position of the reaction can thus be said to be79.6%.

COMPARATIVE EXAMPLE 4

To a 15-ml volume sealed pressure glass reactor were placed 5.0 ml ofisopropanol, 0.521 g of m-cresol (4.81 mmoles) and 0.205 g of sodiumhydroxide (4.81 mmoles). After the reactor was purged with nitrogen, themixture was stirred with heating at 80° C. to form a solution. After thetemperature was lowered to room temperature, 3.58 ml of a solution inisopropanol of formaldehyde purified by sublimation (2.40 mmoles asformaldehyde) was added, and the mixture was purged with nitrogen andstirred with heating at 50° C. for 19 hours to complete the reaction.

The yield was 84.3% based on formaldehyde.

The product was a mixture consisting of 4-hydroxymethyl-3-methylphenol,6-hydroxymethyl-3-methylphenol, 2-hydroxymethyl-3-methylphenol anddimethylol derivatives such as 4,6-dihydroxymethyl-3-methylphenol andthe like. The proportion of the 4-hydroxymethyl-3-methylphenol relativeto the product was 7.3%. At an initial stage of the reaction in which nodimethylol derivative had yet been formed, the ratio of4-hydroxymethyl-3-methylphenol to the product was 12.3%, and theselectivity to the p-position of the reaction can thus be said to be12.3%.

APPLICABILITY IN INDUSTRY

According to the present invention, p-methylolated derivatives of phenolcompounds can be prepared inexpensively and easily. The p-methylolatedderivatives are useful as medicines, agricultural agents andantioxidants, or as raw materials for synthesizing them. Thus, thepresent invention can be applied advantageously to the production ofthese organic compounds.

What is claimed is:
 1. A process for selectively para-methylolating aphenol which comprises reacting a phenol compound and a formaldehydesource in the presence of an alcoholic organic solvent selected from thegroup consisting of an alkanol having 1 to 10 carbon atoms and apolyhydric alcohol having 2 to 10 carbon atoms at a temperature of about0° to 130° C., wherein a quaternary ammonium cation is used as a countercation of the anion of the phenol compound during the reaction in anamount of 0.01 to 10 equivalents based on the phenol compound used andthe reaction is continued until substantially complete to therebyproduce p-methylolated product in a p-isomer/o-isomer ration greaterthan
 1. 2. A process according to claim 1, wherein the phenol compoundis phenol.
 3. A process according to claim 1, wherein the phenolcompound is a substituted phenol.
 4. A process according to claim 3,wherein the substituted phenol is a 2-substituted phenol, a3-substituted phenol, a 3,5-disubstituted phenol, a 2,5-disubstitutedphenol, a 2,3-disubstituted phenol or a 2,3,5-trisubstituted phenol. 5.A process according to claim 4, wherein the substituted phenol is a2-substituted phenol.
 6. A process according to claim 3, wherein thesubstituent of the substituted phenol is an aliphatic hydrocarbyl group,an alkoxy group or a hydroxyalkyl group having 6 or less carbon atoms.7. A process according to any one of claims 1 to 6, wherein theformaldehyde source is formaldehyde, formalin, paraformaldehyde,hemiformals of lower alcohols, or hemiformals of polyhydric alcoholshaving 2 to 5 carbon atoms.
 8. A process according to claim 1 or 2,wherein the quaternary ammonium cation originates from a quaternaryammonium compound which is a tetraalkylammonium hydroxide or a hydroxideform of an anion-exchange resin of quaternary ammonium salt type.
 9. Aprocess according to claim 8, wherein the tetraalkylammonium hydroxideis a tetramethylammonium hydroxide or tetrabutylammonium hydroxide. 10.A process according to any one of claims 1 to 6, wherein the alcoholicorganic solvent is a lower alcohol.
 11. A process according to claim 10,wherein the lower alcohol is ethanol, n-propanol, i-propanol ori-butanol, alone or in admixture thereof.
 12. A process according to anyone of claims 1 to 6, wherein the reaction is carried out by adding thephenol compound in a proportion of 0.1 to 10 moles to 1 liter of thealcoholic organic solvent and the formaldehyde source in a proportion of0.01 to 10 equivalents to the phenol compound.
 13. A process accordingto any one of claims 1 to 6, wherein anion exchange resin particleshaving thereon a quaternary ammonium phenolate comprising the quaternaryammonium salt type anion exchange resin as the quaternary ammoniumcompound and a given phenol compound and the formaldehyde sourcecompound in a proportion of 0.001 to 10 equivalents of the phenolate arereacted in the presence of the alcoholic organic solvent in an amount toensure that the particles are completely immersed in the solvent.
 14. Aprocess according to claim 8, wherein the quaternary ammonium compoundis a tetraalkylammonium hydroxide having up to 6 carbon atoms in eachalkyl group.
 15. A process according to claim 8, wherein the quaternaryammonium compound is the hydroxide form of an anion-exchange resin ofquaternary ammonium salt type.
 16. A process according to claim 1,wherein the amount of said quaternary ammonium compound is 0.1 to 10equivalents based on the phenol compound used.